1. Field of the Invention
The present invention relates to a method of preparing microcapsules. More particularly, the present invention relates to a method of preparing microcapsules containing a biologically active agent.
2. Description of the Prior Art
A variety of methods are known by which any type of compound desired can be encapsulated in the form of microcapsules. In the processes the material to be encapsulated is generally dispersed in a solvent containing a wall forming material. At a single stage of the process, solvent is removed from the microcapsules and thereafter the microcapsule product is obtained. An example of a conventional prior art microencapsulation process is shown in U.S. Pat. No. 3,737,337 wherein a solution of a wall or shell forming polymeric material in a solvent is prepared. The solvent is only partially soluble in water. A solid or core material is dissolved or dispersed in the polymer containing solution and thereafter in a single step, the core material containing solution is dispersed in an aqueous liquid which is immiscible with the organic solvent in order to remove solvent from the microcapsules. Another example of a process in which solvent is removed from microcapsules containing a substance in a single step is shown in U.S. Pat. No. 3,523,906. In this process a material to be encapsulated is emulsified in a solution of a polymeric material in a solvent which is immiscible with water and then the emulsion is emulsified in an aqueous solution containing a hydrophilic colloid. Solvent removal from the microcapsules is then accomplished in a single step by evaporation and the product is obtained. In still another process as shown in U.S. Pat. No. 3,691,090 organic solvent is evaporated from a dispersion of microcapsules in an aqueous medium in a single step, preferably under reduced pressure. Similarly, the disclosure of U.S. Pat. No. 3,891,570 shows a method in which solvent from a dispersion of microcapsules in polyhydric alcohol medium is evaporated from the microcapsules by the application of heat or by bringing the microcapsules under reduced pressure. Another example of a one-step solvent removal process is shown in U.S. Pat. No. 3,960,757.
The problem of the conventional encapsulation techniques is that, especially when they are used to microencapsulate a pharmaceutical agent such as progesterone or norgestimate, the drug loading is a limiting factor. Depending on the physical and chemical properties of the excipient and the agent to be microencapsulated, an attempt to prepare microcapsules with too high of a loading results in incomplete encapsulation, i.e., agent crystals protruding out of the microcapsules or growing in the process medium. A need, therefore, has continued to exist for a technique of preparing microparticles of improved characteristics and of higher quality.